Xia, Xuhua2021-02-172021-02-172021Xia, X. 2021. Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design. Viruses 13(1), 1091999-4915https://pubmed.ncbi.nlm.nih.gov/33466921/http://hdl.handle.net/10393/41782https://doi.org/10.20381/ruor-26004The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created.enCOVID-19S-2PSARS-CoV-2cleavagehydrophobicityisoelectric pointprotein structurespike proteinvaccineCOVID-19COVID-19 VaccinesHumansMembrane FusionMutationProtein BindingProtein DomainsProtein StabilityReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationArticle10.3390/v13010109